It is kproposed to investigate the effects of metals (Cu, Hg, Pb, and Ni) on the structure and functions of murine lymphocytes. This objective will be accomplished through experiments designed to determine the mechanisms by which physiologic and pharmacologic doses of metals alter lymphocyte proliferation, immunoglobulin synthesis, and T-cell helper and suppressor activities, as well as the interactions between the lymphocyte subsets and their factors. In vivo (chronic) and in vitro (acute) exposure to the metals will be compared to investigate the mechanisms involved in the posited metal-induced modulation of the development and differentiation of immunocompetent cells in vivo. Analysis of metal alteration of endogenous lymphocyte surface proteins will aid in evaluating how metals influence the characteristics of the lymphocyte subsets. Analysis of metal-induced alteration of the antigenicity of cell surface self-constituents will aid in assessing the potential development of autoimmune problems. Evaluation of metal-induced modulation of lymphocyte physiology and of the immunoregulatory pathways will aid in the analysis of metal toxicity. Investigation of short- and long-term effects of exposure to low levels of metals will help in identifying the health hazard to certain populations and individuals.